Van Wyk-Grumbach Syndrome is an advanced sexual development in association with primary hypothyroidism. The clinical feature in this syndrome is more consistent with stimulation of the FSH receptor by the markedly elevated TSH levels. Treatment of the hypothyroidism results in a rapid return to normal of the biochemical and clinical manifestations. We experienced a case of Van Wyk-Grumbach Syndrome and report with the brief review of related literature.
Hypothyroidism ; Puberty, Precocious ; Receptors, FSH ; Sexual Development

OBJECTIVE: This study was performed to determine whether the FSH receptor mutation is present in infertile Korean patients with 46,XX premature ovarian failure (POF) women. METHODS: The variant of FSH receptor exon 10 in thirteen 46, XX idiopathic POF and 4 healthy fertile (control) women were studied. Missense mutation in Exon 10 was detected in POF patients and healthy fertile women by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP). RESULTS: The variant types of FSH receptor exon 10 (Thr307Ala; A919G) were found in healthy fertile (control) and POF women. CONCLUSIONS: This mutation may not be specific in POF patients and further study is needed in fertile (control) and POF women.
Exons* ; Female ; Humans ; Mutation, Missense ; Primary Ovarian Insufficiency* ; Receptors, FSH*

Multicystic ovary was first described by Silver in 1958 as a rare case feature of acquired primary hypothyroidism. In 1980, Lindsay reported four girls with hypothyroidism associated with multicystic ovary diagnosed by pelvic ultrasonography. The mechanism of ovarian cyst formation and pseudoprecocious puberty in severe hypothyroidism in childhood are unknown. Increased ovarian sensitivity to GnRH and increased TSH level which acts on FSH receptor is one of the mechanism explained. We report a case of a girl with primary hypothyroidism presented with pseudoprecocious puberty and giant follicular ovarian cyst with torsion.
Adolescent ; Female ; Gonadotropin-Releasing Hormone ; Humans ; Hypothyroidism* ; Ovarian Cysts* ; Ovary ; Puberty ; Receptors, FSH ; Silver ; Ultrasonography

OBJECTIVETo investigate the association between two polymorphisms of follicle stimulating hormone receptor (FSHR) gene and polycystic ovary syndrome (PCOS) susceptibility.

METHODSCase-control studies on relationship of Thr307Ala and Asn680Ser polymorphisms in FSHR gene and PCOS susceptibility were searched from PubMed, ISI web of knowledge, EBSCO, and China National Knowledge Infrastructure (CNKI) databases up to March 21, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effect model based on heterogeneity test in 5 genotype models analyses.

RESULTSA total of 11 studies were included in the Meta-analysis. The random-effect analysis showed Asn680Ser was significantly associated with the reduced susceptibility to PCOS with dominant model (Asn/Asn+Asn/Ser vs. Ser/Ser, OR=0.83, 95% CI: 0.69-1.00), recessive model (Asn/Asn vs. Asn/Ser+ Ser/Ser, OR=0.84, 95% CI: 0.72-0.98), homozygote comparison (Asn/Asn vs. Ser/Ser, OR=0.79, 95% CI: 0.63-0.98), and the allele contrast (Asn vs. Ser, OR=0.87, 95% CI: 0.79-0.97) respectively(P=0.02, I(2)=56.0%), being protective factors for PCOS. However, no significant associations were found between Thr307Ala and PCOS.

CONCLUSIONThere might be a significant association between Asn680Ser polymorphism and PCOS.

Follicle-stimulating hormone (FSH) is synthesized and secreted by the anterior pituitary, which binds to its receptors expressed on the membrane of Sertoli cells in the testis to bring about spermatogenesis. With the development of DNA sequencing technology, FSH SNPs rs10835638 and FSHR SNPs rs6165, rs6166, and rs1394205 were detected, which might directly affect the expression of FSH and activity of FSHR, resulting in male spermatogenic dysfunction. This review focuses on the relationship of FSH and FSHR gene polymorphisms with male infertility.
Follicle Stimulating Hormone ; genetics ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Single Nucleotide ; Receptors, FSH ; genetics ; Sertoli Cells ; Spermatogenesis ; Testis

BACKGROUND: Vitamin is a well-known co-factor for many metabolic processes and its roles in fertility and follicular growth have been studied. Vitamin supplementation is frequently achieved by daily ingestion in the form of a complex capsule. However, the role of single and complex vitamins in in vitro maturation of murine follicles is not fully elucidated. METHODS: In this study, we evaluated the effects of two forms of vitamins. Pure L-ascorbic acid, and multi-vitamin (vitamin C+vitamin B complex) was treated at two different concentrations (50 and 100 µg/ml), to pre-puberty murine follicles during in vitro maturation. To determine the specific stage of growth that is affected by treatment with vitamins, the vitamins were treated from day 0, 4, 9, and 13. Growth of each follicle was assessed by measuring diameters of whole expanded area and of the granulosa cells. Expression of follicular and oocyte growth-related genes and the effect of vitamin on the viability of follicles was assessed using senescence associated β-galactosidase staining. RESULTS: Treatment with vitamins promoted the in vitro growth of murine follicles and the upregulated the expression of granulosa cell- and oocyte-specific genes such as BMP15, Fsh receptor, and GDF9. The proliferation of the granulosa cells was enhanced by the treatment of vitamin. Fifty µg/ml concentration vitamin showed greater effects compared to higher concentration. The viability of in vitro grown follicles was also significantly improved in vitamin-treated follicles. The effects of single L-ascorbic acid and complex vitamin were not significantly different to those of day 4 and day 9 follicles. Vitamins promoted murine follicle development in vitro with different effects on specific growth stage. CONCLUSION: Supplementation of vitamins during in vitro maturation of murine follicles is an efficient strategy for in vitro expansion of follicular cells. These results could be customized to the sophisticated culture of follicles retrieved from aged or cancer-survived female that contain smaller number of follicles with reduced potential to develop into mature follicles.
Aging ; Ascorbic Acid ; Eating ; Female ; Fertility ; Granulosa Cells ; Humans ; In Vitro Techniques ; Metabolism ; Oocytes ; Ovarian Follicle ; Receptors, FSH ; Vitamins

OBJECTIVE: We performed immunohistochemistry for the evaluation of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) expression in the ovarian tumors and examined the blood level of the gonadotropins in ovarian cancer patients to investigate ovarian carcinogenesis process related to gonadotropins. METHODS: Between January 2002 and July 2003, 25 patients with ovarian tumors were treated in the Hallym University Sacred Heart Hospital. 25 ovarian tumors including 7 borderline tumors, 1 sex cord stromal tumor, 1 germ cell tumor, and 16 carcinomas were examined for FSHR, LHR expression by immunohistochemistry. Serum gonadotropins were collected from 13 cases of 25 ovarian tumors who were not taking hormones at the time of blood collection. RESULTS: Followings are results summarized. 1. Mean FSH levels were lower among cases compared with controls. LH levels were lower among cases than controls, but the difference was not statistically significant. 2. The steady decline of FSHR, LHR expression from borderline tumor (86%, 100%) to carcinoma (56%, 43%) is observed. 3. Patients showing significant gonadotropins receptors expression showed lower serum FSH and LH levels when compared with patients with no detectable gonadotropins receptors. CONCLUSION: The presence of FSHR, LHR in ovarian tumors provide additional evidence supporting the relation of gonadotropins and ovarian carcinogenesis. But, this study did not support the hypothesis that pituitary goandotropins increase the risk of ovarian cancer. The decline of receptor expression from borderline tumors to carcinoma suggests that FSH, LH may be needed in early ovarian cancer development. If further studies of gonadal peptides and gonadotropins are done, we can suggest the cut-off value of gonadotropins on ovarian carcinogenesis.
Carcinogenesis ; Gonadotropins* ; Gonads ; Heart ; Humans ; Immunohistochemistry ; Neoplasms, Germ Cell and Embryonal ; Ovarian Neoplasms* ; Peptides ; Receptors, FSH ; Receptors, Gonadotropin ; Receptors, LH ; Sex Cord-Gonadal Stromal Tumors

The clinical models for studying ovary-determining genes may be premature ovarian failure (POF). POF is a condition causing amenorrhea, hypoestrogenism, and elevated gonadotropins in women under 40 years old. FSH receptor, LH receptor, inhibin, GDF-9 (growth differentiation factor-9), BMP-15 (bone morphogenetic protein-15), DIAPH2 (diaphanous gene) and XPNPEP2 (X-prolyl aminopeptidase) genes were proposed as a possible candidate gene, but until recently, only mutations in FSH receptor, LH receptor and inhibin genes have been identified in POF patients. Therefore mutation screening of another POF gene necessary to reveal the principal causative genes of POF. OBJECTIVE: The present study was performed to analyze the mutation of GDF-9 gene in Korean patient with POF and to investigate whether mutation of these gene is a likely main cause of POF. METHODS: Eighty-six women with POF were studied and thirty-six normal women were enrolled as control. Mutation screening of these genes were performed by denaturing HPLC and were confirmed by automatic sequencing. RESULTS: Three different mutations of GDF-9 gene were identified in Korean women with POF; Arg3Cys mutation in one patient, Leu40Val mutation in one patient, Asp57Tyr mutation in 10 patients and 5 normal controls. Arg3Cys mutation and Leu40Val mutation were likely cause of disease. Frequencies of Arg3Cys mutation and Leu40Val mutation were 1.2%, respectively. Asp57Tyr mutation was common polymorphism in Korean women. All mutations was a novel mutation found in the present study. CONCLUSION: POF was resulted by mutations of GDF-9 gene, but mutations of GDF-9 gene are not likely main causes of POF because of low frequency of mutations.
Adult ; Amenorrhea ; Bone Morphogenetic Protein 15 ; Chromatography, High Pressure Liquid ; Female ; Gonadotropins ; Growth Differentiation Factor 9 ; Humans ; Inhibins ; Mass Screening ; Primary Ovarian Insufficiency* ; Receptors, FSH ; Receptors, LH

OBJECTIVE: To determine whether the follicle stimulating hormone(FSH) receptor gene mutation (C566T point mutation) is present in Korean women with premature ovarian failure and normal karyotype. METHODS: Genomic deoxyribonucleic acid(DNA) obtained from 40 patients with chromosomally competent premature ovarian failure and from 30 normal fertile women(control group) was amplified by polymerase chain reaction(PCR). PCR products were digested by the enzyme BsmI and polyacrylamide gel(PAG) elctrophoretic patterns of these enzyme-digested products were analyzed. The direct sequencing of PCR products was also performed. RESULTS: All patients with premature ovarian failure and 30 normal control women demonstrated homozygous, normal alleles with 51- and 27- base pairs fragments in PAG elctrophoresis. The absence of C566T point mutation in both group was confirmed by direct DNA sequencing. CONCLUSIONS: A C566T mutation in FSH receptor gene is rare in Korean women with premature ovarian failure and normal karyotype.
Alleles ; Base Pairing ; Female ; Follicle Stimulating Hormone* ; Humans ; Karyotype* ; Point Mutation ; Polymerase Chain Reaction ; Primary Ovarian Insufficiency* ; Receptors, FSH* ; Sequence Analysis, DNA

OBJECTIVE: To investigate the association of FSH receptor (FSHR) polymorphism at position 680 with outcomes of controlled ovarian hyper-stimulation for IVF-ET in Korean women. Design: Genetic polymorphism analysis. MATERIALS AND METHODS: The FSHR polymorphism was analyzed by PCR-RFLP in 172 ovulatory women below the age of 40 year. Patients with polycystic ovary syndrome, endometriosis, or previous history of ovarian surgery were excluded. RESULTS: Genotype distribution was 41.9% for the Asn/Asn, 47.7% for the Asn/Ser, and 10.5% for the Ser/Ser FSHR genotype group. There was no difference in age of subjects and infertility diagnosis between genotype groups. When the patients were grouped according to their FSHR genotype, the basal levels of FSH (day 3) were significantly different among the three groups (6.0+/-0.3 IU/L (mean+/-SEM), 5.8+/-0.3 IU/L, and 8.6+/-1.2 IU/L for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, p=0.002). The Ser/Ser group showed a higher total doses of gonadotropins required to achieve ovulation induction, and a lower serum estradiol levels at the time of hCG administration compared with other two groups, but the differences were of no statistical significance. The numbers of oocytes retrieved were significantly different among the three groups (8.6+/-0.8, 9.9+/-0.6, and 6.3+/-0.9, for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, p=0.049). Clinical pregnancy rates were 42.4%, 25.9%, and 29.4% for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. CONCLUSION: Homozygous Ser/Ser genotype of FSHR polymorphism at position 680 was associated with decreased ovarian response to gonadotropin stimulation for IVF-ET.
Diagnosis ; Embryo Transfer* ; Embryonic Structures* ; Endometriosis ; Estradiol ; Female ; Fertilization* ; Follicle Stimulating Hormone* ; Genotype ; Gonadotropins ; Humans ; Infertility ; Oocytes ; Ovulation Induction ; Polycystic Ovary Syndrome ; Polymorphism, Genetic ; Pregnancy Rate ; Receptors, FSH*